DESCRIPTION: This research will test the hypothesis that melatonin derived from the pineal gland, modulated by light cycling or derived from foods (phytomelatonin), inhibits hepatoma growth in male and female Buffalo rats. The mechanism to be tested is that melatonin reduces the uptake of the tumor growth-promoting fatty acid, linoleic acid (LA), its metabolism to 13-HODE (13-hydroxy-9,11-octadecadienoic acid), the expression of the fatty acid transport protein, FATP, and the level of cellular glutathione (GSH). Rats will be fed purified diets supplemented with food-derived or synthetic melatonin or will be subjected to light cycling. Blood melatonin levels will be determined. Tumor growth and blood A-V fatty acid differences and tumor fatty acid uptake will be assessed. Biochemical and molecular analysis of the fatty acid transporter, FATP, and of enzymes involved in 13-HODE and GSH production will be determined. This novel hypothesis may provide important information regarding the impact of melatonin on cancer chemoprevention via inhibition of fatty acid uptake and metabolism.